Vänttinen Markku, Nuutila Pirjo, Pihlajamäki Jussi, Hällsten Kirsti, Virtanen Kirsi A, Lautamäki Riikka, Peltoniemi Pauliina, Kemppainen Jukka, Takala Teemu, Viljanen Antti P M, Knuuti Juhani, Laakso Markku
Department of Medicine, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.
J Clin Endocrinol Metab. 2005 Jul;90(7):4249-54. doi: 10.1210/jc.2005-0101. Epub 2005 Apr 26.
The Pro(12)Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene is associated with insulin sensitivity. Obesity is a major risk factor for insulin resistance, but the association of the Pro(12)Ala polymorphism with body weight has been controversial. Furthermore, obesity may modulate the effect of this polymorphism on insulin sensitivity.
The aim of our study was to investigate the effects of the Pro(12)Ala polymorphism on skeletal muscle and adipose tissue glucose uptake (GU) in nonobese and obese subjects.
The design was a cross-sectional study.
The rates of GU were investigated in 124 (72 nonobese and 52 obese; body mass index cutoff point, 27 kg/m(2)) healthy subjects with the euglycemic hyperinsulinemic clamp. Skeletal muscle and adipose tissue GU and skeletal muscle perfusion were measured using fluorine-18-labeled fluorodeoxyglucose, [(15)O]H(2)O, and positron emission tomography.
The rates of skeletal muscle GU were higher in nonobese subjects carrying the Ala(12) allele than in subjects carrying the Pro(12)Pro genotype (P = 0.004), whereas no differences were found in skeletal muscle perfusion between the groups. In contrast, in obese subjects the rates of skeletal muscle GU did not differ between carriers of the Ala(12) allele and carriers of the Pro(12)Pro genotype. No difference in adipose tissue GU was found in either nonobese or obese subjects according to Pro(12)Ala polymorphism.
We conclude that the Pro(12)Ala polymorphism modulates skeletal muscle GU differently in nonobese and obese subjects.
过氧化物酶体增殖物激活受体γ2基因的Pro(12)Ala多态性与胰岛素敏感性相关。肥胖是胰岛素抵抗的主要危险因素，但Pro(12)Ala多态性与体重的关联一直存在争议。此外，肥胖可能会调节这种多态性对胰岛素敏感性的影响。
我们研究的目的是调查Pro(12)Ala多态性对非肥胖和肥胖受试者骨骼肌及脂肪组织葡萄糖摄取（GU）的影响。
本研究为横断面研究。
采用正常血糖高胰岛素钳夹技术，对124名（72名非肥胖者和52名肥胖者；体重指数临界值为27kg/m²）健康受试者的GU率进行了研究。使用氟-18标记的氟脱氧葡萄糖、[(15)O]H₂O和正电子发射断层扫描测量骨骼肌和脂肪组织的GU以及骨骼肌灌注。
携带Ala(12)等位基因的非肥胖受试者的骨骼肌GU率高于携带Pro(12)Pro基因型的受试者（P = 0.004），而两组之间的骨骼肌灌注无差异。相比之下，在肥胖受试者中，携带Ala(12)等位基因者与携带Pro(12)Pro基因型者的骨骼肌GU率无差异。根据Pro(12)Ala多态性，在非肥胖或肥胖受试者中，脂肪组织GU均未发现差异。
我们得出结论，Pro(12)Ala多态性对非肥胖和肥胖受试者骨骼肌GU的调节作用不同。
